In C3H/HeJ mice infected as neonates with Moloney murine leukemia virus (MuLV-M-carriers), autoaggressor lymphoid cells appear in the thymus and the peripheral lymphoid tissues during the course of lymphoma development. These cells are vigorously reactive against normal syngeneic and some allogeneic target cells; they are not reactive against xenogeneic target cells and they also spare syngeneic target cells infected with leukemia viruses. The aggressor cells have been characterized as MuLV-infected, thymus-derived (T) cells. Lymphoma cells arising in MuLV-M-carriers demonstrate identical reactivity. The purpose of the proposed studies is to gain further insight into the phenomenon of MuLV-M-induced autoaggression, its relationship to lymphomagenesis, and its applicability as a model for virus-induced autoimmunity. Employing conventional methods for studying cell-mediated immune responses, we shall attempt to: 1) Further characterize the lymphoma cells arising in MuLV-M-carriers with respect to their immunological markers. 2) Determine whether autoaggressor thymocytes appear before malignant lymphoma cells. 3) Determine whether autoaggressor thymocytes can be triggered after MuLV-infection in vitro. 4) Further understand the relationship between autoaggressor thymocytes and immune suppressor thymocytes in MuLV-M-carrier mice, and their relationship to lymphomas arising in these mice. 5) Determine whether the autoaggressor activity seen in MuLV-M-carriers also occurs in association with lymphomas induced by endogenous MuLV. 6) Determine the possible role of "activated" endogenous MuLV or MuLV gene products in sparing of target cells from kill by MuLV-M-carrier thymocytes.